Remodeling following acute myocardial infarction (MI) is an adaptive mechanism that changes the geometry of the left ventricular (LV) chamber. The present study was designed to determine how this process affects LV size and function and their response to hemodynamic changes. MI was created in 23 adult sheep by arterial ligation on the anterior or posterior coronary circulation. Animals were studied either 24 hours (group I; n=10) or 6 months (group II; n=13) later. Similar coronary occlusion procedures were followed in both groups to achieve equivalent size of MI. In each study, real-time 3-dimensional echocardiographic (RT3D echo) images were obtained in the open-chest anesthetized animals at baseline, during angiotensin II and sodium nitroprusside (SNP) infusion, and during partial ligation of the inferior vena cava. LV volumes were measured off-line from RT3D echo images using an interactive tracing technique based on a Silicon Graphics workstation. Baseline LV end-diastolic (EDV), end-systolic (ESV) and stroke (SV) volumes, and ejection fraction (EF) in Group I vs Group II, respectively were as follows: EDV (ml) 44.4+/-6.9 vs 64.7+/-6.6 (p<0.0001); ESV (ml) 15.6+/-3.3 vs 35.0+/-4.9 (p<0.0001); SV (ml) 28.8+/-4.9 vs 29.7+/-4.3 (p=0.67); EF (%) 65+/-5 vs 46+/-5 (p<0.0001). There was no difference between the two groups in the response to angiotensin II administration or inferior vena cava ligation. However, SNP induced an increase in SV only in group I (P=0.005); consequently, SV measured during SNP infusion was significantly greater in group I compared to group II animals (33.2+/-2.1 vs. 27.6+/-2.6 ml; P=0.01). Thus, remodeling following MI leads to LV dilation and reduced global function without changing SV. Afterload reduction positively affects LV function only during the early phases of MI and therefore is more likely to be beneficial at this stage than after the remodeling process has been completed.